Department of Biological and Environmental Sciences and Technologies, University of Salento, I-73100, Lecce, Italy.
Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, I-00161, Rome, Italy.
Reprod Toxicol. 2021 Jan;99:48-55. doi: 10.1016/j.reprotox.2020.11.011. Epub 2020 Nov 26.
The widespread cultivation of genetically modified organisms (GMOs) led to a widespread use of selective herbicides to which GMOs are resistant, thus increasing the concern about human exposure to them. Glyphosate (GLY) and glufosinate ammonium (GA), the active principles of the main formulations, have been investigated for their effects on human health, mainly cancer and reproductive toxicity. However, little is known about their effects on the molecular mechanisms related to sperm quality. To investigate the effects of GLY and GA on mitochondrial respiration efficiency, we took advantage of our already established ex vivo human sperm mitochondria assay. Since spermatozoa are highly regulated by sex steroids, we tested at first testosterone (T), di-hydroxytestosterone (DHT), 17β-estradiol (E2) and progesterone (P4). Then, we tested the effects of GLY and GA and of the hormone-like flavonoid quercetin (QRC) in a dose-dependent manner. The 0.1-1000 nM concentration range has been considered because it covers both the sexual hormones physiologically relevant concentrations (10 nM), triggering endogenously hormone-dependent signaling pathways, and the estimated (nM range) QRC dietary intake. Subsequently, co-incubation experiments were carried out with the two herbicides in the presence of 10 nM of each sex steroid and QRC. We found that: i) DHT and QRC are able to significantly reduce mitochondrial functionality at concentrations ≥ 10 nM; ii) GLY and GA negatively affect mitochondrial respiration efficiency; iii) in the presence of 10 nM DHT, the negative effect of GLY was increased; iiii) DHT, QRC and GA target mitochondria by using a mechanism different from GLY.
广泛种植的转基因生物（GMO）导致广泛使用抗此类生物的选择性除草剂，从而增加了人们对人类接触这些生物的担忧。草甘膦（GLY）和氨甲基膦酸（GA），是主要制剂的有效成分，已经对其对人类健康的影响进行了研究，主要是癌症和生殖毒性。然而，关于它们对与精子质量相关的分子机制的影响知之甚少。为了研究 GLY 和 GA 对线粒体呼吸效率的影响，我们利用了我们已经建立的体外人精子线粒体测定法。由于精子受性激素的高度调节，我们首先测试了睾酮（T）、二氢睾酮（DHT）、17β-雌二醇（E2）和孕酮（P4）。然后，我们以剂量依赖的方式测试了 GLY 和 GA 以及类激素黄酮槲皮素（QRC）的作用。考虑到 0.1-1000 nM 的浓度范围既涵盖了生理相关浓度的性激素（10 nM），从而引发内源性依赖激素的信号通路，又涵盖了估计的（nM 范围）QRC 饮食摄入量，所以进行了测试。随后，在存在每种性激素和 QRC 的 10 nM 的情况下，进行了两种除草剂的共同孵育实验。我们发现：i）DHT 和 QRC 在浓度≥10 nM 时能够显著降低线粒体功能；ii）GLY 和 GA 会对线粒体呼吸效率产生负面影响；iii）在存在 10 nM DHT 的情况下，GLY 的负面影响增加；iiii）DHT、QRC 和 GA 通过不同于 GLY 的机制靶向线粒体。
